YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis.
Dev Cell
; 42(5): 462-478.e7, 2017 09 11.
Article
em En
| MEDLINE
| ID: mdl-28867486
ABSTRACT
Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium-specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton and that activated YAP/TAZ induce a transcriptional program to further control cytoskeleton dynamics and thus establish a feedforward loop that ensures a proper angiogenic response. Lack of YAP/TAZ also results in altered cellular distribution of VEGFR2 due to trafficking defects from the Golgi apparatus to the plasma membrane. Altogether, our study identifies YAP/TAZ as central mediators of VEGF signaling and therefore as important regulators of angiogenesis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Transdução de Sinais
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Neovascularização Fisiológica
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Fator A de Crescimento do Endotélio Vascular
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Proteínas Adaptadoras de Transdução de Sinal
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha